Intermittent furosemide administration in patients with or at risk for acute kidney injury: Meta-analysis of randomized trials

BACKGROUND: Furosemide is the most common loop diuretic used worldwide. The off-label administration of furosemide bolus(es) for the prevention or to reverse acute kidney injury (AKI) is widespread but not supported by available evidence. We conducted a meta-analysis of randomized trials (RCTs) to investigate whether bolus furosemide to prevent or treat AKI is detrimental on patients' survival. METHODS: Electronic databases were searched through October 2017 for RCTs comparing bolus furosemide administration versus any comparator in patients with or at risk for AKI. The primary endpoint was all-cause longest follow-up mortality. Secondary endpoints included new or worsening AKI, receipt of renal replacement therapy, length of hospital stay, and peak serum creatinine after randomization. RESULTS: A total of 28 studies randomizing 3,228 patients were included in the analysis. We found no difference in mortality between the two groups (143/892 [16%] in the furosemide group versus 141/881 [16%] in the control group; odds ratio [OR], 0.84; 95% confidence interval [CI], 0.63 to 1.13; p = 0.25). No significant differences in secondary outcomes were found. A significant improvement in survival was found in the subgroup of patients receiving furosemide bolus(es) as a preventive measure (43/613 [7.0%] versus 67/619 [10.8%], OR 0.62; 95% CI, 0.41 to 0.94; p = 0.03). CONCLUSIONS: Intermittent furosemide administration is not associated with an increased mortality in patients with or at risk for AKI, although it may reduce mortality when used as a preventive measure. Future high-quality RCTs are needed to define the role of loop diuretics in AKI prevention and management. TRIAL REGISTRATION: The study protocol was registered on PROSPERO database for systematic reviews (Registration no. CRD42017078607 - http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42017078607).